About this Author

College chemistry, 1983

The 2002 Model

After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
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August 18, 2009

Schematic Notation for Biology?

Posted by Derek

I see that there's a serious effort underway to standardize biochemical diagrams. About time! As a chemist, I don't mind admitting that I've been confused by many of these things over the years. As the current task force points out, one reason for that is that there are too many processes that all get drawn the same way: with a curved arrow. Enzymatic cleavage? Allosteric regulation? Product inhibition? Nucleic acid splicing? Enzyme activation? A curvy arrow should do nicely. And if the same scheme includes several of those phenomena at once, then we'll just use more arrows, making sure, of course, that they're all exactly the same size and style.

The new proposal seems to be based on the ideas behind electrical circuit diagrams and flow-chart conventions, and will attempt to convey information through several means (box shapes, arrow styles, etc.) I hope it, or something like it, actually catches on, although it'll take me a while to get used to translating it. Actually, what will take a while is getting used to the idea that biological diagrams are supposed to be imparting information at all. I've been trained in the other direction for too long.

As an engineer who finds himself in this industry, I cannot agree more. Process flow diagrams are more or less standardized in the chemical process industry. I can look at a layout for a plant pushing out resin and read it just as easily as one for processing waste water.

Since grad school, I've had to read these papers on cellular metabolism and disease progression, and they were very confusing at first. I've spent many a time staring at a figure in a paper thinking to myself: I'm sure this made sense to the authors. Then I'd go find someone and ask them the standard way to interpret one thing or another only to be told that there was no standard.

I'm sure it's my biases showing here, but basically these processes are just little unit operations. So I for one welcome our new visio-based overlords.

While I am all for good conventions that aid consistency and understanding I can see such things leading to us chemists thinking we now know more than we actually really do about a particular biologic pathway or system. Worse still I likewise see when it gets in the hands of MBA types such descriptive diagrams will take on granite carved status the belies the complexity that is being illustrated.

Don't get your hopes up. There have been several similar efforts before. This group is engineer- and mathematical modeler-heavy, and, while I know and respect several of the people behind the initiative, I don't hold out much hope for them converting actual bench biologists. I hope I'm wrong, but I suspect that most bench biologists don't think of their pathways as circuits, and don't want to represent them as such. I think the best that this group can hope for is to standardize the diagrams that appear in papers describing mathematical models of cells.

There are some bits of notation that have become fairly standard in the general biological literature (e.g., -| means inhibition of a pathway), though.

Biologists haven't even truly standardized protein naming, and I long ago gave up any hope of that happening. I just build my databases to allow multiple names for any protein.

This sounds fantastic. As someone with an electrical engineering background who has migrated to biomedical engineering/life sciences, I think more systematic notation could aid research, especially as things move toward computational and systems biology approaches. We often taken notation for granted, but without it we couldn't do math or listen to Bach compositions hundreds of years after they were written.

This is stupid. There are simply too many different kinds of biological interactions. To do this properly, you would need a different symbol for every single pairwise interaction (and these symbols would constantly be changing as our understanding evolves) which would make it completely useless. You can criticize biology if you want for not being more logical or easier to codify, but that's mostly the fault of Nature not biologists. Cells are not roundbottoms!

Not mentioning that many biology protocols are black magic - some additives are used there over and over because the Asian postdoc who originally made the assay work thought that adding this stuff into his witches' brew could help, and ever since they published the paper no-one was brave or curious enough to test whether the additive actually does something...

Along the lines of improving things -- abolish the word 'modulate' in biological papers. It sounds far more impressive than it is and is basically a weasel word. Then you have to dig and dig through the paper to find if 'modulate' means increase or means decrease the (flow through/function) of a given (biochemical/physiological) pathway. Modulate rarely means both.

Asian postdoc was used in the example just to add an extra layer of mystery about the reasoning behind the magic recipe. Maybe I should have written "a long-gone cryptic dude who made this to work" to be more politically correct.

Hmmmm. If the purpose is simply to distinguish one type of process or interaction from a limited number of alternatives then that could be useful, IF the number of interactions would be relatively limited. Unfortunately, the complexity of many biological signaling pathways and processes means that you'd have to remember a substantial number of symbols, which would confuse or even defeat the purpose. Also, CMCguy has it right, this will tend to exacerbate the already over-developed reductionist tendencies in the industry, as illustrated by the comment about "little unit operations" in post #1.

I think the best notation would just be a curly arrow with a bubble stuck at the halfway mark; for printed materials the bubble could be just a little bigger than the circular stickers used to label the tops of eppendorf tubes. Write in the relationship on the sticker, slap it on. Six months later when the data has changed put an updated sticker over the first. Might be prudent to have a bunch of stickers with '?' pre-printed on them.

I, for one, preferred it with "asian postdoc". It lent the special ingredient an exotic air of oriental mystery. Also, I used to share a bench with a Japanese postdoc who labeled all his bottles in Japanese to keep people from stealing his reagents.

Learning to understand and talk about this stuff (or convincingly pretending to) is part of getting a bachelor's degree in biochemistry (etc.). We all pick it up from the likes of Stryer and TiBS. Actually producing one or two of these diagrams is how you get your PhD. And recycling one of them through several different designs is a central activity on the way to tenure.
All you can say about these things is that there is evidence at least for a somewhat coherent syntax, at least within local dialects (a lab, a field) but also for plenty of meaningless BS. It's never been properly studied or made explicit, and since that also applies to the actual language that scientists use, I don't see any prospect of that changing.
Linguists, semiotics people and graphic artists all live on different planets with plenty of BS of their own, and though there are probably some of their ideas that need to be applied to this problem, it's beyond the possibilities of a human life to try to get these enormously disparate disciplines together.
A committee of engineers trying to get prescriptivist about this will not get any traction among the people who make and use these things. I'd predict a success rate similar to Esperanto.